- REITER'S DISEASE* BY A. H. HARKNESS Joint-Director Endell Street Clinic, St. Peter's and St. Paul's Hospital (Institute of Urology); Consultant in. Venereal Diseases to- St. -Charles' Hospital; the Civil Consultant in Venereal Diseases to the Royal Navy

Reiter's disease is characterized by a clinical joint. This appears to me to have been a clear syndrome consisting of a primary abacterial ure- case of the dysenteric syndrome. -Description of thritis of venereal origin, bilateral conjunctivitis, the syndrome, until the oetiology is established, polyarthritis, frequently balanitis, and sometimes would be facilitated if a distinct differentiation keratodermia blennorrhagica; cardiac and other were made between cases of venereal and those of manifestations have also been described.- The dysenteric origin. I advocated in 1947 that the, itiology is unknown. term " Reiter's disease," or better still " dysenteric There is an almost identical syndrome associated arthritis," be applied only to the latter, and that with the various types of dysentery (the primary the former-those of venereal origin-be described focus of infection in these cases is the bowel and as " non-gonococcal polyarthritis " or " the non- not the urethra) which is probably the same disease. gonococcal syndrome." Much confusion would, There are also certain other diseases and reactions I am convinced, be avoided by such a distinction. due -to treatment which may simulate the syndrome The venereal syndrome, as we know it today, very closely. was recognized many years before Reiter published In my experience true Reiter's disease is one in his case, indeed a case in which the syndrome was which the primary focus of infection is an abacterial complete was described by Launois in 1899. In urethritis of venereal origin with blood-borne this instance there had been five previous attacks complications. (In none of my cases have I of gonorrhoea, the syndrome developing during an observed dysenteric symptoms nor have any of attack of urethritis in which gonococci could not them shown a previous history of dysentery.) The be found in the discharge or urine, the latter being syndrome may be complete or incomplete. It is heavily infected with Bacillus coli. commonly pyrexial, sometimes runs a protracted Priority in the description of the syndrome course, and often recurs after short or long periods urethritis, conjunctivitis, and arthritis, however, of remission. In my series two separate attacks should be accorded to Sir Benjamin Bilodie, who in occurred in twenty-four patients, three in four, 1818 gave a full description of one typical case and and four in one: the syndrome was never complete referred in some detail to four others.t in more than one attack. Two of the original forty-four cases of abacterial It has frequently been reported to me by my male urethritis of venereal origin described by Wmlsch nurses at St. Charles's Hospital that patients with in 1916 developed blood-borne complications, one the syndrome, including those acutely ill, invariably rheumatic pains in both knees and ankles, and the have voracious appetites. other bilateral conjunctivitis two days- after the From the many references to Reiter's - disease urethral discharge was noticed. Inflammation of which have appeared. recently in the literature, it the eyes reappeared four months later following seems that several misconceptions exist on the intercourse with the same woman. Wwelsch (1916) subject. Much of the confusion would' appear considered that the eyes were infected by fingers to be due to the fact that the disease bears Reiter's contaminated with the urethral secretion. name. In his case, reported in 1916, the illness was In dealing with this subject it is difficult to know ushered in with severe abdominal pain, diarrhoea how many of the clinical entities of the syndrome and blood-stained stools, followed eight days later are necessary before it is possible to make a by a purulent -urethral discharge with bilateral diagnosis of Reiter's disease. Should only the conjunctivitis. On the ninth day there was an cases in which the syndrome is complete be re- acute polyarthritis, and six weeks later numerous viewed, or should the primary focus of infection, pustules were noted in the region of the left hip together with one, two, or three of the blood-borne An Address to the Medical Society for the Study of Venereal Diseases, April 29, 1949. t This was brought to my notice by my friend Robert Milne. c 185 186 BRITISH JOURNAL OF VENEREAL DISEASES TABLE I complications of bilateral conjunctivitis, arthritis, and keratodermia blennorrhagica. Details of this series are given in Table I. I shall also include twelve cases in which the gonococcus was present

0 in the urethral discharge before the commencement U, of treatment for urethritis (Table II). It is pre- sumed that penicillin destroyed the gonococcal element in the urethral discharge and that the residual abacterial infection caused the subsequent 2 + + + - - - development of blood-borne complications. 6oplcaios182S + warn+- + hiicuini th decrip All the patients included in Tables I and II were tin?Gnuciiisi omnyml andehm males. The disease is extremely rare in females; 25 + + - + - - + 8 + - - + -. indeed there -are many workers who maintain that 2 + - - - - + - it never occurs in women. In 1945 I was able to 1 + - - - + - - fihid only nine cases of keratodermia blennorrhagica recorded in women (Harkness, 1945). I have had complications warrantt their inclusion in the descrip- two cases in which a non-gonococcal cervical tion? Conjunctivitis is commonly mild ~tnd ephem- discharge (cultures for " L" organisms being eral; the balanitis and keratodermia blennorrhagica positive in both) was associated with polyarthritis (unless generalized) are often inconspicuous and and typical lesions of keratodermia blennorrhagica symptomless; the three conditions are therefore (one also suffered from bilateral conjunctivitis); easily overlooked as they have been in tnany cases and I saw recently a similar case with Harman. I of polyarthritis referred to me for treatment. On have had other cases of polyarthritis in women with the other hand the arthritic manifestation of the a non-gonococcal cervicitis in which " L " organisms disease is invariably disabling and was present in have been cultured, but the absence of skin lesions all the cases described in the literature except the made the diagnosis extremely difficult. As will be third case of Stuihmer's series, Roth's case, and seen later, a number of cases have been reported thirteen of mine which are described below. in women in association with the dysenteric Many of the doubtful cases described in the syndrome. literature, including that of Lojander (1927), in Sequence of Syndrome which there was no evidence of infection in the urinary tract, are commonly associated with atypical In my series of cases in which it was possible to skin lesions, usually hyperkeratotic rupial patches observe the progression of the disease, conjunctivitis and not nodules. However, in one of my cases, in was noted one to eighteen days (commonly six) which there were three attacks, the syndrome was after the appearance of the urethral discharge, and complete during the first illness and in the third a arth,ritis one to six days later. In two cases unilateral iritis and polyarthritis occurred with no arthralgic pains in several joints were noted before signs or symptoms in the urinary tract. the onset of conjunctivitis. Definite articular In my description of the venereal syndrome I involvement did not occur until a few days later. shall include all cases ofprimary abacterial urethritis Bilateral conjunctivitis associated with arthralgic together with one or more of the blood-borne pains and myositis with no subsequent development ofarthritis was observed in two cases: conjunctivitis TABLE II was not noted in two other cases associated with PRIMAR-Y MIXED INFECTIONS (GONOCOCCAL AND NON- arthralgia only. GONOCOCCAL) It must be emphasized, however, that in many cases, including some in which the syndrome has No. Abacterial Ocular Kerato~- progressed to include keratodermia blennorrhagica, of gonococcal mani- Arthritis bernnrrhagica- conjunctivitis has been either absent or so mild cases festations that it has been overlooked. This smay be the explanation for the two cases with unilateral iritis 7 + - which were not observed until two weeks after the 3 + + onset of arthritis. + Balanitis is commonly noted soon after the onset of arthritis and always before the appearance of No cases from the pre-penicillin era are included. Blood-borne complications occurred one to twenty-six days after successful the rash. Early lesions of keratodermia blennor- penicillin therapyfor the gonococcal element in the urethral discharge. rhagica were noted in one case on the same day as RElTER'S DISEASE 187 the arthritis, but in all other cases it was not observed instrument, is frequently observed in this type of until at least a month after the onset of the disease. urethritis, whereas " organic " stricture requiring dilatation treatment, observed in seven cases, was Urethritis and other Manifestations in the probably due to previous gonococcal inflammation. Urinary Tract The primary focus of infection, in the majority Acpte Onset of Urethritis is distinguished by a of cases, is a non-gonococcal abacterial urethritis. profuse muco-purulent or purulent urethral dis- This is commonly ushered in with signs and symp- charge simulating gonorrhoea, and severe pain on toms of subacute (rarely acute) inflammation, micturition which may precede the onset of urethral though occasionally the urethra is the seat of discharge; urethroscopy shows a generalized red primary 'nixed infections of both gonorrhoea and and inflamed mucous membrane with no excres- abacterial urethritis. In the latter, penicillin therapy cences or infiltrations. In view of the acute eliminates the gonococcal element of the urethral symptoms cystoscopy has been carried out in'only discharge but the non-gonococcal element persists. two of my cases before the commencement of In such circumstances acute arthritis, with or treatment: on both occasions it revealed acute without the development of other blood-borne generalized cystitis. The cystoscopic picture is complications, may follow days or weeks later. similar to that of abacterial pyuria and this is, in In none of these cases have I been able to demon- all probability, the same disease (Harkness and strate gonococci in the residual urethral discharge, Henderson-Begg, 1948), the acute generalized vesiculo-prostatic secretions, synovial fluid, or cystitis being a local complication of a primary early lesions of keratodermia blennorrhagica, and urethritis the infective agent of which may become for this reason I regard the complications as being blood-borne to cause Reiter's disease. of non-gonococcal causation (see Table II). It is I have treated five cases of primary abacterial reasonable to assume that there may also be urethritis, four subacute and one acute, in which I primary mixed infections with an abacterial com- have seen the complete syndrome of Reiter's disease ponent and organisms other than gonococci, but subsequently develop: uncertainty prevails owing to the lack of specific In cases with subacute onset the urine is clear therapy for the elimination of the bacterial element. with threads in the first glass and clear in the In view of this I have excluded from my series a second; though investigations will commonly few cases in which urethritis was considered to be reveal a symptomless prostatitis. In those in bacterial (non-gonococcal). which the onset is acute there is obvious involve- ment of the posterior urethra; it is in this type Mild Onset of Inflammation shows itself as a of urethritis that heematuria is sometimes observed. subacute abacterial or Welsch urethritis. This is The urethral discharge in eight oT my cases (one characterized by a long incubation period (five to with the complete syndrome) was hemorrhagic, thirty days), mildness of symptoms, a clear, and the urine contained blood. Upper urinary tenacious urethral discharge (this is occasionally tract investigations during convalescence revealed mnuco-purulent, rarely purulent), and, in 60 per dilated renal pelves in most cases. Colby (1944) cent. of cases, a typical urethroscopic picture: describes three cases of Reiter's disease, the first this, in the early stages, shows wedge-shaped with hematuria and prostatic abscess, the second excrescences that appear to lie superficial to the with hamaturia, right hydronephrosis, and prostatic mucous membrane of the ,anterior urethra with no abscess (which developed after nephrectomy), and obvious involvement of the subepithelial connective the third with haematuria and dilatation of both tissue. They are seen chiefly on the roof and renal pelves and ureters. Miller and McIntyre lateral walls of the urethra, the base of each being (1945) also reported two cases with hematuria attached to the mucous membrane with the pointed associated with lesions of upper urinary tract, one or blunted, acute-angled edge lying free and pro- with pyelitis and the other with dilated left renal truding into the urethral lumen. Later the excres- pelvis. cences become flatter and resemble cobble-stones that have been likened to the nodules of trachoma. Conjunctivitis and Ocular Manifestations It must be emphasized that this urethroscopic Inflammation of the conjunctiva commonly picture is present in a large percentage of cases involves both eyes and, though in many the in- with blood-borne complications. flammation is more marked in one eye, I have seen " Urethroscopic" stricture, in which the lumen it unilateral in two cases only. It is usually of the urethra is not diminished in calibre and associated with episcleritis and in most cases, as presents no obstruction to the passing of a large already mentioned, is mild. '(It may occasionally 188 BRITISH JOURNAL OF VENEREAL DISEASES be severe, and was so in fourteen of my cases: in Small joints of feet .. 25-0 six of them it was the only blood-borne complica- Small joints of hands .. .. 18-6 tion.) Mid-tarsal .. . . 10.0 Recurrent attacks (often in conjunction with rise Wrist 9-2 Periostitis 8-0 of temperature, acute exacerbations of pain, and Sacro-iliac 5-4 swelling in joints) are to be observed in cases Shoulder 4-6 resistant to treatment, and I have seen as many as Elbow 3-8 three attacks during a three months' illness. Uni- Sterno-clavicular lateral. or bilateral iritis occurred in eight of my Acromio-clavicular series, but in the first illness it was preceded by Intervertebral .. . . 0-4 conjunctivitis in all but two. Unilateral iritis, Hip .. .. i0-4 duripg subsequent relapses of the disease, may be As in blood-borne infections due to gonorrhoea, the only ocular lesion. acute local complications such as epididymitis, Herpes of the conjunctiva and cornea has been acute prostatitis, etc., were not observed. in any of reported also, but some of these lesions may have the cases. been ocular manifestations of keratodermia blen- Radiographs of joints during the first month of norrhagica since vesicles, subsequently developing the disease usually show an increase in joint space into erosions, appeared concomitantly with crops only, but when they are carried out later they often of typical lesions in other parts of the body. reveal diffuse or localized areas of osteoporosis, Arthritis especially in the region of the articular ends of the small joints of the, hands and feet. Spindle-shaped Arthritis, thd most constant blood-borne com- swellings, sometimes large, in the region of the plication, was absent in 13 (11 per cent.) of my 126 interphalangeal and metacarpo-phalangeal joints are cases. In six the urethritis was associated with commonly due to inflammatory changes in the conjunctivitis; in two -with conjunctivitis and soft tissues: it is exceptional in such cases for arthralgic pains; in two with arthralgic pains only; radiographs to show any abnormality. However, in two with tenosynovitis involving the extensor I have observed bony changes, sometimes late in tendons of the wrist; in one with inflammation the first illness but more often during recurrent of the right sub-deltoid bursa. Arthritis was also attacks. abseht from the syndrome in the third case of StUhmer's series in which an acute non-gonococcal In one patient generalized arthritic changes were seen urethritis was associated with high fever and in both hands. The proximal interphalangeal joint of bilateral conjunctivitis. It was also absent in the middle finger of the right hand also showed gross changes with loss ofjoint space, and there was periostitis Roth's case that showed tenosynovitis of the of the first and second phalanges. extensor tendons of the right great toe and kerato- In another patient there was laxity of the ligaments dermia blennorrhagica. of the right knee, allowing mild subluxation backwards In all but twenty-one of my cases the onset of with the knee in the flexed position, and with relaxed arthritis was acute, making it impossible to dis- muscles. The metacarpo-phalangeal joint of middle tinguish them from those in which a gonococcal finger of left hand showed the same, but more severe, etiology was presumed to be certain. The cases laxity of ligaments. There was destruction of the in which it was subacute occurred-more frequently anterior part of the head of the third'metacarpal bone in recurrent attacks of the disease. This complica- with osteoporosis of the head and the base of the adjacent phalanx; also periostitis of the shaft of two tion is commonly polyarthritic. It was mon- bones on either side of the joint, and forward subluxation arthritic on seven occasions only, but .in these of the phalanx on the metacarpal. arthralgic pains with no swelling or limitation of I have previously reported a case (Harkness, 1945) in movement were observed in other joints. Further which there was marked laxity of the ligaments of the joints became involved during treatment in 8 per affected joints, especially the right knee, in which there cent. of the cases: in recurrent attacks the same was subluxation backwards of the right tibia, and also joints were frequently involved. Previous joint displacement outwards and internal rotation. injury or disease, predisposing to localization of Radiographs of the knees of another patient (with a infection, was rarely observed. fifteen-year history of recurrent attacks of arthritis associated with conjunctivitis or iritis and urethritis) The order of frequency of the joints involved, showed very irregular contours- of femoral and tibial including periostitis of the os calcis, was: condyles: the bone showed irregular sclerosis beneath Joint % the articular cortex. The joint space was narrowed Knee ...... 70 3 (indicating erosion of cartilage) a>nd there were large Ankle ;...... 55.4 marginal osteophytes. There was almost complete REITER'S DISEASE 189 fibrous ankylosis but radiographs showed no evidence mon in uncircumcised subjects in which the prepuce of bony ankylosis. The case was one of osteo-arthritis completely covers the glans, and it was noted in supervening on destruction from acute inflammation. 43 per cent.. of my cases. It consists of heaped In another case with a twelve-year history of recurrent up attacks of non-gonococcal urethritis associated with layers of scales which, when removed, leave a arfhritis there was extensive new bone formation in the weeping surface due no doubt to exposure of the soft tissues over the median femoral condyles and corium. Fresh scales soon appear, but to a lesser similar changes not so well marked over the external extent especially when the parts are cleansed with condyles. saline followed by the application of a bland I have seen six further cases, all occurring during the powder. second, third, or fourth attack, in which osteo-arthritic In the first place 'there are multiple areas of changes were observed. inflammation, separated by normal mucous mem- Periostitis of the os calcis with sub-calcanean brane. These soon coalesce to form one large spurs associated with plantar fasciitis was observed- serpiginous and sharply defined patch commonly in fourteen cases. In one, spurs developed on both situated either in the coronal sulcus or on the feet during an attack of gonococcal urethritis, posterior two thirds of the glans, though occasion- cpnjunctivitis, and arthritis. They proved resistant ally the area involved surrounds the external meatus. to treatment and were excised with excellent results The hard nodular lesions of keratodermia blennor- that showed immediately. However, a further rhagica may also appear on th- glans, usually in attack of abacterial urethritis, polyarthritis with circumcised subjects, either alone or in association painful heels, and keratodermia blennorrhagica with soft patches. developed in the same patient five years later when a radiograph revealed that the two large spurs had Keratodermi Blennorrhagica reappeared. - Keratodermia blennorrhagica occurred in thirty- In no cases did the infective process in joints five of my series; in thirty-three in conjunction progress to cause suppuration. As already men- with primary abacterial urethritis and in two with tioned, bursitis (the only metastatic complication primq mixed infection: it also occurred in three on one occasion) was observed in five further cases females. The development ofvesicular," pustular," associated with arthritis. Tenosynovitis in the two and nodular lesions on the soles of the feet were cases already referred to also occurred alone. observed in seven cases. Bauer and Engleman (1942) in their investigations on There are two types of lesion, the hard para- the pathology of the joint changes, excised a small keratotic nodules with their three distinct phases- portion of synovial tissue (during the thirteenth week vesicle, pustule; and nodule-, and the soft, limpet- of the disease) from the left knee of a man aged 23 with like parakeratotic patches consisting of many layers the venereal syndrome. There were areas of suggested of scales, often heaped up centrally and resembling villous formation in the suprapatellar pouch (one of rupia, the former being more characteristic of the which was excised) with slight thickening and marked disease. Confusion in injection of the synovial membrane. Sections showed diagnosis commonly occurs the synovial membrane to consist of several layers of when the latter appear unaccompanied by nodules, cells with an excess of lymphocytes and plasma cells as is commonly the case in the dysenteric syndrome in the intercellular spaces: only an occasional leucocyte and arthropathic psoriasis. The nodules show a was seen. An cedematous subepithelial connective predilection for the soles of the feet, but there is tissue was crammed full with a dense cellular infiltration occasionally a generalized distribution. with focal collections of lymphocytes and plasma cells In a previous communication in May 1944 forming a cuff surrounding the capillaries. Scrapings (Harkness, 1945), I submitted evidence that kerato- from the synovial membrane did not reveal the presence dermia blennorrhagica was a complication of of inclusion bodies. On the other hand pathological non-gonococcal urethritis. I maintained that when investigations carried out by Wepler (1942) on a man with the dysenteric syndrome who died from intercurrent it occurred in association with gonorrhea there disease, showed cedema of the synovial membrane with was a mixed infection of both diseases, though the complete absence of its cellular lining: the joint capsule gonococcal element played no part in the appear- and periarticular tissue were infiltrated with lympho- ance of the eruption. Since then unlimited supplies cytes, but there were no changes in cartilage or bone. of penicillin have become available, with the result that in mixed infections nowadays the gonococcal Balanitis element is quickly eliminated, leaving behind it Balanitis, usually called " balanitis circinata" in a residual non-gonococcal urethritis. Since my American literature, is seen frequently in association review of the cases in which gonococci were said to with arthritis, but it may occur before the onset of have been found in the skin lesions, Gately (1945) blood-borne complications. It is especially com- claims to have demonstrated Gram-negative diplo- 190 BRITISH JOURNAL OF VENEREAL DISEASES cocei on several occasions in his case, but cultures The erythrocyte sedimentation changes were a poor were omitted so that definite bacteriological proofis guide to success or failure of treatment, this being lacking. No organisms were found in a watery possibly due to the relapsing nature of the disease. urethral discharge of four days' -duration, the skin Only slight insignificant falls after both fever lesions on the hands and feet showed a marked therapy and myochrysine were noted in patients inflammatory reaction and certainly were by no acutely ill, but in mild apyrexial forms of the disease means typical of keratodermia blennorrhagica. a normal erythrocyte sedimentation rate was not The reader is referred to my previous communication uncommon after treatment. A fall was noted in (Harkness, 1945) for a more detailed description of cases receiving sodium salicylate gr. 30 six-hourly, this complication. in one from 67 to 26, and in another from 22 to 6. Pyrexia In the two cases treated with streptomycin there was a rise, one from 63 mm. to 125 mm. and the As already mentioned, I have observed all stages other from 104 mm. to 121 mm. Dienes and his of the development of the complete syndrome in collaborators (1948) also noted that the erythrocyte five cases. The temperature in these was normal sedimentation rate remained high for considerable when a non-gonococcal discbarge was the only periods after streptomycin had been administered. manifestation of disease, but after the development -In two cases ofmyositis associated with an abacterial of blood-borne complications the temperature in all urethritis the erythrocyte sedimentation rate was registered 100' F. or higher. normal both before and after treatment. Pyrexia associated with the syndrome is extremely variable. Fifteen per cent. were apyrexial through- The Dysenteric Syndrome out the period of observation but they may have It has been known for many years that dysentery been pyrexial before admission under my care. may be complicated by obstinate attacks of arthritis, Swiging temperatures which varied between 1000 indeed Manson-Bahr (1943) states that Celius and 1030 F. were recorded in 32 per cent. of the Aurelianus described the condition (rheumatismus series (it was so in all cases with a genalized intestinalis cdim ulcere) at the beginning of the fifth eruption), all such patients being extremely T and century. Krauiter (1871) reported both arthritis cachectic. An occasional slight rise in temperature and conjunctivitis in association with the disease, was observed in the other cases. and Markwald (1904) the first case with urethritis, Cardiac Manifestations conjunctivitis, and arthritis three weeks after the commencement of an attack of Shiga dysentery. Two of my cases developed tachycardia with Singer (1915), in a series of six hundred cases of pulse rate which varied between 120 and 150 over bacillary dysentery, observed several cases with periods of five to six weeks during the acute phase myalgia and conjunctivitis, seven with arthritis, of the disease; however, the cardiologist could and only one with urethritis. Feissinger and detect no cardiac lesions. Leroy (1916), in a study of an epidemic of bacillary Lever and Crawford (1944) reported a cardiac dysentery on the Somme in 1916, noted, a few lesion suggestive of a myocardial infarct in their months before Reiter, the same clinical syndrome first case in which a generalized rupioid eruption (syndrome conjunctivo-uretro-synovial) in four of was associated with urethritis. Feiring (1946) their cases. reported the prolongation of the auricular-ventricu- The majority of the cases develop the syndrome lar conduction in two cases. One of Warthin's after apparent recovery from dysentery but, as in cases (1948) had symptoms suggestive of acute Reiter's case, it may also occur during the acute myocarditis but, following treatment with strepto- phase of the disease. Polyarthritis has been mycin, the heart rhythm and sounds became normal. described in association with the various types of bacillary dysentery-more often Shiga and Flexner Erythrocyte Sedimentation Rate -and cases have also been reported by Moorhead The erythrocyte sedimentation rate, by the (who noted sAx), by Feissinger and Leroy (1916), Westergren method using a 200-mm. tube, was and by Manson-Bahr (1945), in which it appeared carried out at weekly intervals on all my cases, a during or after an attack of amoebic dysentery. figure of 12 mm. being regarded as the upper Gabrielle and others (1938) reported a case of non- normal limit. In a large proportion of cases the gonococcal urethritis and arthritis in a patient test registered 100 mm. or more, a rate of 135 mm. suffering from diarrhoea due to Giardia lamblia. being not uncommon, and the lowest recorded rate The frequency ofarthritis in epidemics of bacillary was 18 mm. Generally speaking the highest rates dysentery varies considerably, as shown by the favt occurred in the severest types of the syndrome. that in one epidemic (1897) in the Fiji Islands REITER'S DISEASE 191 10 per cent. of the cases developed this complication, syndrome triad was complete in 233 (69-8 per cent.). whereas in a further epidemic in the same colony There were no cases in which urethritis was the thirteen years later (observed by Manson-Bahr only symptom, although it was the initial symptom (1920), there weu none. The syndrome triad is in a slightly larger percentage of cases (23-9 per in fact more frequently observed incomplete. cent.) than arthritis (23-3 per cent.) arthritis Gounelle and others (1940) described fifty cases occurred in 97-3 per cent. of arthritis that occurred during a mild epidemic Smyly states that the synovial fluid from cases of Flexner dysentery, of which 46 per cent. were of dysenteric arthritis occasionally shows the associated with urethritis -and 68 per cent. with Bacillus dysenteriak in both smears and cultures, bilateral conjunctivitis. In Kokko's series (1945) but I know of no cases with the triad of symptoms due to the Flexner bacillus, 111 of 555 cases were in which this has been so. The blood serum in a suffering from conjunctivitis, and only three with small percentage of cases agglutinates the type of purulent urethritis, but ninety more patients organism responsible for the enteritis, as in the complained of pain on micturition: the syndrome cases reported by Markwald (1904), Beiglb6ck triad was complete on three occasions only. (1943), Cimbal (1942), Paronen (1948), and Gounelle In Cimbal's (1942) series 82 per cent. were and others (1940). Positive agglutination tests suffering from conjunctivitis and 47 per cent. from with the synovial fluid have also been reported, urethritis. In Paronen's series of 344 cases of and, Smyly maintains, in a titre even higher than Reiter's disease (310 males and 34 females) in that of the blood serum, whereas Gounelle and his which 71 per cent. developed during the acute collaborators (they obtained strongly positive phase of dysentery due to Flexner bacillus, the reactions in the blood serum up to 1/400 in three

TABLE III AGGLUTINATION TESTS WITH DYSENTERY ORGANISMS OF NORMAL SERA AND SERA FROM CASES OF URETHRITIS 1 192 BRITISH JOURNAL OF VENEREAL DISEASES cases, 1/320 in one case, slightly positive up to Diagnosis 1/50 in one case, and negative in one case) con- As will be seen from the above descriptions, the sidered that the results in the synovial fluid were venereal and dysenteric syndrome are, in all similar to those-of the blood. probability, the same disease awl caused by the In Paronen's series agglutination tests on the same infective agent, the portal ofentry in the former blood serum were positive in 61 of 132 examined, being the urethra and in the latter the diseased in titres varying between 1 in 80 to 1 in 640, and mucous membrane of the large intestine. on the joint fluid in eight of the twenty-four In some cases reported in the literature, as in the examined. one described by Thiers and Joly (1948), it is Arthritic and ocular manifestations are similar difficult to determine whether the syndrome is in most respects to those already described in venereal or dysenteric. These authors state that association with the venereal syndrome. A very only the third attack of urethritis, iritis, and detailed investigation of the bony changes was arthritis was associated with dysenteric symptoms, carried out by Gounelle and his collaborators but the blood did not agglutinate dysentery bacilli. x-ray examinations during the first month were It must be noted, however, that the venereal always normal (as it was in all of Cimbal's cases) syndrome has rarely been reported in women, but two to three months later changes were often whereas many such cases have occurred in associa- observed, especially in the extremities of the bones. tion with the dysenteric syndrome. Indeed it was Osteoporosis was the most frequent finding, but so in thirty-four of the 344 cases described by in some cases there were bony erosions causing Paronen. One of Paronen's cases occurred in a indistinct bone margins, a condition which also boy aged two and a half years. Two-further cases occurs in association with the venereal syndrome in boys aged 12 and 4 respectively were reported and is described as a periosteal reaction. These by Shiga (1904) and Florman and Goldstein (1948). workers also observed osteophytes in eight of their No cases of the venereal syndrome have been cases and, in view of this, consider that dysenteric reported in children. In the dysenteric syndrome, arthritis should be renamed post-dysenteric osteo- too, recurrences are infrequent and the skin arthritis. Paetzel (1928) reported a case in which manifestations are commonly parakeratotic patches the radiograph of a toe showed atrophy of a joint and not nodules. with partial ankylosis. Before proceeding it is necessary to mention Urethritis has been noted in only a small per- that quite a large number of workers consider, centage of cases of dysenteric arthritis, and the wrongly I think, that the syndrome has no connection urethroscopic picture has not been included in with venereal disease. Indeed an annotation in any of the descriptions. Involvement of the body the British Medical Journal of Dec. 7, 1946, states of the testicle and epididymis occurred in nine of emphatically that the disease bears no relation to Paronen's series: six with pain and tenderness sexual intercourse. but no swelling, one with acute orchitis, and two The synovial fluid is the same in both syndromes. with epididymo-orchitis. In my cases it was commonly straw-coloured and somewhat turbid and the cell exudate consisted of Skin Eruptions in association with the dysenteric both polymorpho-nuclear leucocytes and lympho- syndrome are extremely rare and-usually consist cytes, usually with a predominance of the former, of the soft parakeratotic rupia-like patches seen but sometimes of the latter. No organisms occasionally in the venereal syndrome: it occurred (including M. tuberculosis) were seen in- smears, only twice in Paronen's series of cases. Balanitis and cultures were always sterile. Similar findings has also been noted by several workers, and in have been reported in the dysenteric syndrome. Paronen's series it occurred in 32-9 per cent. usually Smyly (1937) states that the Bacillus dysenteriak has in association with urethritis. Epistaxis was re- been cultivated in the synovial fluid but very few ported by Gounelle and his collaborators in a cases have been reported in the literature. large number of their cases and was considered to The fact that the blood serum and synovial fluid be due to an increase in the coagulation time of may agglutinate dysenteric bacilli does not necess- the blood. arily indicate that the syndrome is due to dysentery: Recurrences of arthritis are infrequent, and it may -simply show that the patient has or has had four of the ten described by Paronen were dysentery. In the same way a positive gonococcal preceded by diarrheea. However, this worker complement fixation reaction obtained in cases noted recurrence of urethritis in six, and of with primary mixed infections of both gonorrhrea conjunctivitis in fifty cases during treatment for and abacterial urethritis may only indicate that arthritis. the patient has or has had gonorrhcea. REITER'S DISEASE 1193 Agglutination tests with dysenteric organisms of 0-1 c.cm. of the diluted antigen resulted, after were carried out for me by Bushby on blood sera five to seven hours, in the development of a wide of seventeen of my cases of venereal origin (six in area of erythema with marked induration of the which the syndrome was complete) and on four skin. Both control guinea-pigs and rabbits failed normal subjects. There were no significant agglu- to react to the antigen. tinations of organisms of the dysentery groups, the An extensive trial, promising in the first place, antigens used being Shiga, Flexner X, Y, 103, and was abandoned, owing to a fairly high percentage 119, Newcastle, Schmitz, and Sonne. of false positive results. . The occurrence of arthritis, with or without Serological Tests (agglutination and complement other blood-borne complications soon after the fixation) were carried out in some of my cases-all elimination of gonocecci from the urethral secre- with negative results* tions, demands a thorough search for these organ- The disease may be confused' with arthropathic isms in the vesiculo-prosta-tic secretions and synovial psoriasis, acute rheumatism in adults, septicaemia, fluid before a diagnosis of Reiter's disease can be Stevens-Johnson syndrome, Behcet's syndrome, made. It is essential that the aspiration of joints ninth-day erythema of Milian, toxic manifestations is carried out as soon as possible. So far I have ofsulphonamides, serum sickness, secondary syphilis, failed to detect gonococci in such cases. and arthritis in association with certain fevers (for - Difficulties in diagnosis due to primary mixed example, typhoid"fever). infections may also arise in countries in which lymphogranuloma inguinale is prevalent. Frei Differential Diagnosis tests, carried out with either mouse brain antigen Arthropathic Psoriasis.-Many cases of arthro- or lygranum on a large number of my cases, were pathic psoriasis have been described, wrongly I negative in all. think, as Reiter's disease. The joint condition is- Professor Bedson kindly carried out cormplement one of rheumatoid arthritis, noted only in eight of fixation tests for antibodies of the lymphogranuloma my venereal series (it was considered to have inguinale virus on the blood sera of twenty of my supervened after destruction by acute inflammation), cases, nine in which the syndrome was complete and on eight occasions -in the dysenteric series of and eleven incomplete. Complete fixation occurred Gounelle and his collaborators. Difficulties in in only one of the former group (at a dilution of diagnosis commonly arise from the fact that the 1 in 32) and in two of the latter (one at a dilution skin eruption sometimes consists of rupia-like of 1 in 16, the other at 1 in 64): Frei tests were lesions indistinguishable both clinically and histo- negative in all three cases. It' is interesting to note logically from the soft parakeratotic patches of that no antibodies were detected in the blood serum keratodermia blennorrhagica; indeed'it is possible of a case of uncomplicated subacute abacterial that both diseases may be caused by the same urethritis in which indisputable virus inclusions infective agent. However, 'in some of the cases were present in urethral scrapings. described in the literature, as in the first of L6he and Rosenfeld's series, the lesions developed Skin Sensitivity Tests.-Storm-Mathisen (1946) subsequently into those .of psoriasis vulgaris. The described a skin test for -Reiter's disease which syndrome in a large majority of the cases of arthro- employed a mixture of joint exudate and gland 'pathic psoriasis consists ofrheumatoid arthritis and emulsion obtained from a case of this disease. A skin lesions only, and is very rarely associated with red papule (12 mm.), increasing slightly in size up urethritis or conjunctivitis, indeed I have never to the eighth day and persisting for several months, seen a case with inflammation of eyes or urethra. hours after intradermal developed forty-eight I recently saw -with Muende a man aged 45 with a inoculation in five cases diagnosed as suffering two-years history of two or three very small lesions of from Reiter's disease. A negative result followed- psoriasis vulgaris situated on the elbows. It is interesting the inoculation of eleven controls, including three to note that two months after an attack of urethritis of with polyarthritis rheumatica. venereal origin which was resistant to sulphonamide and I employed, for skin testing, a phenolized sus- penicillin therapy, the eruption became generalized. It pension of" L " organisms prepared by Henderson- was then characterized by three types of lesions: psori- Begg. Intradermal tests were, in the first place, asis vulgaris, psoriasis rupioides, and keratotic nodules carried out in normal subjects and it was determined (chiefly on the soles of the feet), which were indistinguish- of 1: 20 this rise to able from those of keratodermia blennorrhagica: that at a dilution antigen gave urethral washings were positive for " L" organisms. no more reaction in the normal skin than the control inoculation 0-5 per cent. phenol saline. In Acute rheumatism in young adults may render' sensitized guinea-pigs the intradermal inoculation For scrological methods seeHarkness and Henderson-Begg (1948). 194 BRITISH JOURNAL OF VENEREAL DISEASES diagnosis extremely difficult. This is due to its after the commencement of treatment in those not pyrexial onset, to arthritis which is polyarthritic previously sensitized to the drug. and migratory but never suppurative, and to the Secondary Syphilis is rarely a source of error. cutaneous manifestations. Several cases admitted Recently, however, a case was admitted under my under my care with a diagnosis of Reiter's disease care with a diagnosis of Reiter's disease, ini which have reacted favourably to salicylates and 1 have a non-gonococcal urethritis due to meatal chancre also had four cases of the disease, two in which the was associated with suffused conjunctivx, swelling syndrome was complete, transferred to me after of both knee joints, and a generalized psoriasiform several months treatment in medical wards for acute syphilide. rheumatism. Typhoid fever may be complicated by urethritis, Septicwmia.-Cases with the syndrome triad have conjunctivitis, and arthritis, and cases have been been described in association with staphylococcal reported in which a diagnosis of Reiter's disease has septicaemia and chronic meningococcal septicaemia: been made. one of them (Biland, 1905) is wrongly reported in the literature as a case of Reiter's disease. The Serum Sickness following administration of serum primary lesion was an osteomyelitis of an acromion during an attack of dysentery is stated by Manson- -process with secondary foci of bursitis, urethritis, Bahr to clear up spontaneously after a few days, but epididymitis and subcutaneous abscesses: Staphy- the delay in its appearance and the fact that it may lococcus aureus was isolated from all foci ofinfection. be associated with fever, rash, and arthritis must Junghanns (1918) also reported the case ofa boy aged sometimes render diagnosis extremely difficult. 16 with the syndrome triad which was regarded by him as a case of staphylococcal septicxemia. There Aetiology was a previous history of boils fourteen days before Reiter isolated -a spirochite in the blood of his the onset of the illness, but organisms were not case and, in view of this, called the disease ''spiro- demonstrated in any of the lesions: the case, in chetosis arthritica," but in this respect all subsequent my opinion, was one of Reiter's disease. workers have failed. Macfie in 1917 reported the The clinical syndrome of chronic meningococcal case 'of a native of the Gold Coast with a haemorrha- septicemia which consists chiefly ofmuscle and joint gic urethral discharge containing large numbers of pains, joint effusions, and recurrent skin eruptions actively motile spirochaetes associated with arthralgic usually of the erythema nodosum type, associated pains and severe iritis in both eyes. The condition, with relapsing or intermittent fever, may also be which reacted favourably to galyl and mercury, is mistaken for Reiter's disease. wrongly referred to in the literature as a case of Stevens-Johnson Syndrome, with its febrile onset, Reiter's disease. urethritis, balanitis, ocular lesions and skin eruption, Various types of organisms, including staphylo- may be associated with arthritis as in the cases cocci, diphtheroid bacilli, streptococci, B. coli, and described by Lever (1944). It may then be difficult pneumococci, have been isolated in the urethral to distinguish from Reiter's disease. discharge by various workers, due no doubt to inadequate cleansing of the meatus before the Behcet's Syndrome, which consists of severe taking of specimens. Stuihmer (1921) found Gram- recurring eye lesions, aphthous ulcers on oral and positive bacilli in the four cases he described in genital mucous membranes, and skin eruptions, 1916, but did not consider them to be responsible may also be associated with urethritis and acute for the disease. No- organisms are seen in smears, arthritis as it was in the cases reported by Schmidt and cultures on ordinary media are sterile in a large (1940) and Cavara (1940). majority of the cases when thoroug4 cleansing of Milian's Ninth-day Erythema, with its pyrexial the meatus has preceded the taking of specimens: onset, suffused conjunctivw, scarlatiniform (some- it is always so in my experience, provided no local times papular) eruption, and swollen and painful treatment has been administered. joints may simulate Reiter's syndromo, and the In my opinion there is no doubt that the venereal differential diagnosis is even more difficult when it syndrome is contracted usually by normal sexual develops during treatment of primary abacterial intercourse and occasionally by sodomy, and that the urethritis (Harkness, 1948). primary focus of infection (an abacterial urethritis) Toxic Manifestations of Sulphonamides.-As sul- occurs in the urethra (Harkness, 1945). Recurrences phonamide therapy is prescribed frequently in of the disease invariably follow sexual intercourse, non-gonococcal urethritis it is as well to remember but it is admitted that in some cases the infective that toxic reactions, similar to those of ninth-day agent may have remained latent during the inter- erythema, sometimes appear seven or more days vening period and re-activation of infection. may REITER'S DISEASE 195 have been caused by an additional factor, for Harkness and Henderson-Begg (1948) isolated example, trauma, as has been shown by Burnet "L " organisms in twenty-one (38 per cent.) of (1945) to be the case in recurrences of herpes fifty-seven cases of subacute abacterial or Waelsch simplex. Both the venereal and dysenteric syndromes urethritis, in five (50 per cent.) of ten cases of acute are, in my opinion, due either to a virus or pleuro- abacterial urethritis, and in seven (17 per cent.) of pneumonia-like organisms. forty-one cases of Reiter's disease: only seven of The portal of entry of the infective agent in the the latter presented the complete syndrome, and two dysenteric syndrome is presumed to be the diseased (29 per cent.) gave positive cultures. A much higher mucous membrane of the large intestine. The percentage of positive cultures in Reiter's disease various dysenteric organisms do not cause the dis- was obtained when urethral washings were carried ease but it is possible that they arecontaminated out during the acute phase of the disease, and many by the infective agent. On the other hand, the failures occurred in cases in which admission to infective agent may be normally present in the large hospital was delayed. intestine and the advent of ulceration in dysentery Giemsa-stained smears were examined from all enables it to reach the blood stream and set up my cases, and in many of those in which cultures complications in remote parts of the body. In were positive for " L " organisms epithelial cells possible support of this theory is the fact that free- were seen with the cytoplasm packed with large living strains of pleuropneumonia-like organisms numbers of small bluish- or purple-staining bodies have been isolated in sewage (Laidlaw and Elford, which showed marked pleomorphism: spherules, 1936) and manure (Seiffert, 1937), but it is admitted ovoids, rickettsia-like forms, and elementary-like that the former workers, and also Beveridge (1943), bodies were observed, with a high proportion of failed to detect them in normal human faces. On ring-like forms showing wide morphological varia- two occasions, once by Henderson-Begg (Harkness tion: these bodies were also noted lying free, both and Henderson-Begg, 1948) and once by Bushby dispersed and in small clusters. (1947), pure cultures were obtained from anal swabs Though absent during intervening periods, " L" of two contacts of my cases of Waelsch urethritis organisms have been isolated by Bushby in urethral in which the disease had been contracted by sodomy. washings of several of my patients during recurrent I have recently isolated organisms in an anal swab attacks of the disease. In four such cases in which taken from a normal individual, and also in a swab it was possible to examine contacts cervical swabs from the pelvo-rectaljunction taken during sigmoido- were also positive. In this respect it is interesting to scopy from a man aged 75 with fiTcal impaction. note that in one of the cases reported by Dienes Smith (1942) and Dienes and Smith (1942) were and his collaborators (1948), " L" organisms iso- the first to isolate " L " organisms in the urethral lated in the prostatic secretions during three recurrent discharge from cases of uncomplicated abacterial attacks were absent during the intervening periods. urethritis and Reiter's disease, and in 1948 these Florman and Goldstein (1948) are the only work- organisms were isolated in the synovial fluid of two ers who have attempted to incriminate " L " cases of Reiter's disease by Dienes and his collabora- organisms in the dysenteric syndrome. They failed tors, and of one by Warthin. So far I have been to isolate these organisms or a virus in the urethral unsuccessful in isolating " L " organisms in the discharge, conjunctival secretion, and synovial synovial fluid from five patients, and from the skin fluid of their case. lesions of four. There are many other workers who believe in a In my address to the Medical Society for the virus etiology but so far the evidence brought for- study of Venereal Diseases in May, 1944, I recorded ward has been scanty. the finding of inclusion bodies, possibly a virus, in We have failed to cultivate a virus on the chorio- the scrapings from the urethra, conjunctiva, and allantoic membrane of chick embryos, in mouse skin lesions. At the time of these investigations the brain inoculation, and in tissue culture, and so far previous work concerning human strains of pleuro- no other workers have been successful. In this pneumonia-like organisms in the urogenital tract respect it must be remembered that attempts to was not known, but as the elementary bodies were cultivate the virus of inclusion conjunctivitis from accompanied often by rings, suggesting that the the eyes of babies have also been unsuccessful. rings were developing from the granules, it was Dodd and others (1938) showed that aphthous considered that the bodies were possibly a phase in stomatitis in infants and young children is in most the life cycle of " L " organisms. If the " L" cases due to the virus of herpes simplex and a virus organisms were saprophytes then it is not unlikely has recently been shown by Buddingh (1946) to be that both " L" organisms and virus were seen responsible for a similar disease associated with together. diarrhoea in children. Strains of the virus are 196 BRITISH JOURNAL OF VENEREAL DISEASES maintained by serial passage from cornea to cornea Although the etiology of the disease is still of rabbits, but, unlike primary herpetic stomatitis, uncertain, the fact that a high percentage of positive no inclusions have been found.- In the discussion cultures for " L " organisms is obtained in the types following Buddingh's paper on this subject Sabin of non-gonococcal urethritis associated with the stated that these inclusions would probably be disease, their absence from normal cases, their demonstrated in serial sections. On this occasion disappearance with successful treatment, their recur- Dodd also reported that she had obtained positive rence in re-infections, their presence in a high corneal inoculations in rabbits with vaginal swabs percentage of contacts, and the fact that they have taken from the mothers of the children suffering been isolated in the synovial fluid, all tend to support from the disease, Buddingh had observed similar the conclusion that organisms of this group may be results with the urethral discharge and oral and responsible for the venereal syndrome. It is admitted conjunctival secretions of a typical case of Reiter's that serological tests do not bear this out, but disease. negative results cannot be regarded as strong Dunham and his collaborators (1947) isolated a evidence against the incrimination of " L " organ- filterable agent pathogenic for mice from the isms, as little is known of their antibody response urethral and conjunctival discharge of their case of in the human being.' It may be that antibodies are Reiter's disease in a man aged 23. Suspensions ofthe present in low concentrations, and for such short urethral discharge and conjunctival secretion (in periods that they are not demonstrable by the heart infusion broth and 10 per cent. beef serum) relatively crude methods - at present available. were each inoculated into the allantoic fluid of However, I do maintain (and there are experts in twelve-day embryonated eggs, twelve eggs being virus diseases who agree with me) that some of the used for each suspension. After being sealed with bodies I have demonstrated in scrapings from paraffin the eggs were incubated for forty-eight urethra, conjunctiva, and skin lesions- in Reiter's hours and then chilled for two hours; when the disease are a virus and not " L" organisms. The allantoic fluid from each series was pooled and inclusion bodies seen in these lesions are morpho- filtered through a Seitz E.K. filter. Twenty mice logically indistinguishable from each other, a fact were inoculated intraperitoneally with 0-1 ml. of that points very strongly to a common virus one of four different saline dilutions with the filtrate causation. It is a comparatively easy matter to derived from the urethra and a like number with demonstrate inclusion bodies in inclusion conjunc- that from the eye: twenty mice also served as tivitis in babies, and the difficulty in demonstrating controls. Sixty per cent. of the mice injected with them in scrapings from urethral mucosa is almost material from the eye and urethra developed con- certainly due to the fact that the extreme sensitivity junctivitis: the eyes ofthe controls were all normal. of this structure prevents the taking of adequate It should be mentioned that certain workers, specimens. including Creecy and Beazlie (1948) stress the im- portance of focal infection. In the two cases des- Treatment cribed by Creecy and Beazlie an acute exacerbation The primary focus of infection in the venereal of signs and symptoms followed the removal of foci syndrome being the urethra, perhaps it will not be ofinfection, in one the extraction of a tooth with an out of place if I stress here the importance of apical abscess and in the other tonsillectomy for adequate treatment of this focus in the prevention septic tonsils. Iii my opinion the occurrence of such of blood-borne comnplications. exacerbations is due entirely to the protein shock It was my practice in the pre-sulphonamide era effect of the bacteriaemia, and it has been noted in to treat all cases of primary urethritis, gonococcal many of my cases following the extraction of teeth and non-gonococcal, with twice-daily urethro- during the course of the disease. It does not signify vesical irrigations of potassium permanganatre or that the causal agent is present in these foci of oxycyanide of mercury, and none of these patients infection. to my knowledge subsequently developed blood- Other -workers maintain that the disease is an borne complications. Nowadays, the majority of allergic one. Thiers and Joly (1948) collected the venereologists, including myself, omit local treat- urethral discharge in the first 5 ml. of urine passed, ment for gonorrhoea. During the last year I have and injected 0 5 ml. of this solution intradermally. observed fifteen cases in which penicillin has No reactions occurred at the injection site, but a eliminated the gonococcal elemnent from the urethral severe systemic reaction with high fever and an acute discharge, but the persistence of a non-gonococcal- exacerbation of the arthritis followed, and in view of diseharge has been follo ed by metastatic com- this the author regarded the disease as an allergic plications. I therefore consider that all cases of process. primary non-gonococcal and residual post-gono- REITER'S DISEASE 197 coccal urethritis should be treated with urethro- striking. In one the result was equal to that obtained vesical irrigations and that, when these are efficiently with fever therapy, but in the others fever therapy carried out, blood-borne complications will not was necessary to effect a cure. Beneficial effects of arise. gold therapy may be non-specific and may be due Powell and others (1946) showed that strepto- to the rise in temperature which commonly occurs mycin protected rats and mice from developing for an hour or more after each injection; and this arthritis after injection in the pad with animal strains may be overlooked with a four-hourly chart of " L" organisms, and flushby (1947) found that (Harkness, 1947). "L " organisms of human origin were sensitive to The following is the treatment I have carried out low concentrations of the antibiotic. Therefore,. if during the last ten years, and, until streptomycin pleuropneumonia-like organisms are proved to be becomes available, I shall continue on the same responsible for the disease, streptomycin should lines. be the drug of choice. I have treated two cases with Treatment of the primary focus of infection streptomycin. Both received 10 g. only (0-25 g. consists of twice-daily urethro-vesical irrigations six-hourly for ten days). In the first case an excellent with oxycyanide of mercury, 1 in 6,000. Urethro- result was obtained, but no beneficial effects were scopy will reveal both the presence of urethral noted until a few days after the completion of stricture and the persistence of infiltrations, and in treatment. The other case, in which the syndrome such cases dilatations are necessary. Blood-borne was complete, the same dosage was ineffective. complications commonly react favourably to non- Another case (not included in this series) received specific protein therapy, mild or severe. During the 20 g. (0 5 g. six-hourly) and developed typical lesions first week of the illness it is my usual practice to give of keratodermia blennorrhagica during treatment. three intramuscular injections of aolan, each of Warthin (1948) states that the effects of strepto- 10 ml., and if results are satisfactory the injections mycin in the treatment ofchronic prostatitis due to are repeated during the following week. Unsatisfac- infection with " L " organisms were so striking that tory results demand more severe protein shock he treated four cases of Reiter's disease, three for therapy with sharp rise in fever. I prefer fever seven days with a total daily dose of 4 g., and one induced either by the intravenous injection of triple with 2-5 g. daily for ten days. Warthin states that typhoid vaccine (T.A.B.) or pyrifer (Bacillus coli the results were " not conclusive but still sufficiently vaccine). Five bouts of fever are usually given, and encouraging to warrant further use of-this form of in relapsing cases it may be necessary to repeat the therapy." Improvement in the first case occurred course: coupled dosage also may be called for. during the first week following streptomycin (as in Harman recently treated a case, in which the my first case), but in the third and fourth cases the syndrome was complete with chloromycetin (2 g. beneficial effects of treatment were, in my opinion, three times for one day followed by r g. three dramatic: the discharge ceased, the urine cleared, times daily for seven days). During treat- pain in the joints ceased, and fluid in the knees was ment further joints became involved; the tem- absorbed during-treatment. perature, which was already high, rose higher, and On the other hand Dienes and his collaborators a fresh crop of skin lesions of keratodermia (1948), in the treatment of six cases, noted improve- blennorrhagica appeared. I know of no cases- ment during and immediately after streptomycin treated with aureomycin. (4 g. daily for thirteen days), and " L" organisms Assessment of the effects of treatment is difficult disappeared from the secretions but inflammation (a few cases improve with rest alone) unless dramatic in joints persisted for considerable periods -and, as results are obtained. Penicillin and the sulphona- already noted, the erythrocyte sedimentation- rate mides are, in my hands, always ineffective. Large did not fall. These workers state that the drug does doses of salicylates (30 gr. four-hourly) are some- not prevent recurrences of the disease. This has times followed by excellent results, but this may be been my experience also, as.one of my two patients due to mistaken diagnosis. has since had a relapse after intercourse with his Local treatment of the affected joints consists in wife, who was still harbouring "L" organisms. rest and partial immobilization with sand-bags for Findlay and his collaborators (1940) showed that the lower and a sling for the upper limbs. On no organic gold salts also protected rafs and mice from account should immobilization be by splints or developing arthritis-after injection of" L " organisms plaster-of-paris, as such measures will eventually in the pad. Willcox and others (1947) found gold cause adhesions and ankylosis. Radiant heat baths salts curative in two patients with Reiter's syndrome, for twenty minutes, twice daily, give considerable but the results I have obtained in the treatment of relief when the pain is severe, and aid resolution. eight cases with myochrysine have not been so As soon as the acuteness subsides, massage of the 198 .BRITISH JOURNAL OJF VENEREAL DISEASES muscles above and below the joints, combined with Florman, A. L., and Goldstein, H. M. (1948). Arthritis, conjunctivitis and urethritis (so-called Reiter's syn- passive and later active movements, helps consider- drome) in a four-year-old boy. J. Pediat., 33, 172. ably in restoring function. Friihwald, R. (1928). So-called spirochetosis arthritica Local treatment for the eyes consists of gutta (Reiter, 1916). Urol. cutan. Rev., 32, 7. hyoscine, @5 per cent. twice daily, and sulpha- Gabrielle, H., Hugenot, G., ard Duval, M. (1938). Lyon Med., 162, 299. cetamide, 30 per cent. four-hourly: also boracic Gateley, J. R. (1945). 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DISCUSSION ON REITER'S DISEASE In answer to a question from the President, Dr. DR.' CHFSNEY stated that during recent months, in Harkness said that he used Giemsa's stain when addition to the routine investigations of female patients demonstrating inclusion bodies. at the Endell Street Clinic, cultural examinations for " L" organisms in vaginal and cervical secretions have DR. JoNES said that at Endell Street Clinic cultures for also been carried out. It is difficult at the present L"L organisms were positive in 131 cases of urethritis moment to describe exactly the clinical picture in the in the male; In a series of sixty-three cases of primary female or to state the significance and relationship of non-gonococcal urethritis twenty-six (41-2 per cent.) pleuropneumonia-like organisms to other infections of were found to be positive: this percentage would have the female genital tract. So far Bushby (who has carried been higher but for the inclusion of several cases of out the cultures) has been unable to differentiate between bacterial (non-gonococcal) urethritis. Six contacts of pathogenic, and non-pathogenic strains. On the other this group attended, and in all of them vaginal and hand Edwards has succeeded in doing so in bovine cervical swabs yielded positive cultures. strains. In a series of fifty-seven cases of gonorrhoea, nineteen Cultural examinations for " L " organisms were (33 per cent.) were found to be positive. Seven (63-6 positive in fifty-three of the seventy-six cases investigated. per cent.) of eleven cases of residual post-gonococcal Positive cultures were recorded in: urethritis yielded positive cultures: the only contact 15 of 28 cases of non-gonococcal cervicitis; examined was also positive. 14 of 19 cases of non-gonococcal cervicitis and tricho- Eleven patients were treated with streptomycin, the monas vaginitis ; dosage varying between 0-5 and 1-5 g. daily for ten 5 of 7 cases of gonococcal cervicitis; days. Cultures showed that five (45 4 per cent.) re- 5 of 7 cases of gonococcal cervicitis and trichomonas mained positive on completion of treatment. Twenty- vaginitis; four other patients received only urethro-vesical irriga- 1 of 2 cases of syphilis and non-gonococcal cervicitis tions for seven to fourteen days. Cultures after treat- and trichomonas vaginitis ; ment showed that twenty (83-3 per cent.) of these had 1 of 1 case of syphilis and non-gonococcal cervicitis; become negative. 5 of 5 cases of syphilis and gonococcal cervicitis;